Montserrat Pujol | Universitat de Barcelona (original) (raw)
Papers by Montserrat Pujol
International Journal of Molecular Sciences, Apr 29, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Colloids and Surfaces B: Biointerfaces, Aug 1, 2023
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019
Lipid domains have been obtained using Langmuir-Blodgett films (LBs) and giant unilamellar vesicl... more Lipid domains have been obtained using Langmuir-Blodgett films (LBs) and giant unilamellar vesicles (GUVs). Three membranes compositions were chosen, the canonical DOPC: DOPS (3:2)/SM/CHOL (1:1:1), the more physiological one: DOPC: DOPS (3:2)/SM/CHOL (2:1:1) and another one with more phospholipid content: DOPC: DOPS (3:2)/SM/CHOL (3:1:1). All systems were well characterized by π-A isotherms. As the (SM/CHOL (1:1:1)) concentration increases, the membrane fluidity decreases as demonstrated by the compressibility modulus and area per molecule values. Lipid domains morphology was examined by confocal microscopy. Images corroborated the presence of two liquid immiscible phases: a phospholipid-enriched L d phase and a sphingomyelin enriched L o phase. GBV-C peptide membrane interaction was examined using P6-2VIR576 peptide and tryptophan (Trp) fluorescence spectroscopy. P6-2VIR576 increased the fluidity of lipid monolayers and bilayers making hard to distinguish the L d /L o edges. Its capacity to inhibit the action of the fusion peptide of human immunodeficiency virus (HIV-1 FP) on membranes has been demonstrated. 1. Introduction Eukaryotic cell membranes can exhibit lipid clusters in rafts with different compositions and molecular packing. These rafts play an important role in the assembly of enveloped viruses [1,2]. The human immunodeficiency virus (HIV-1) is one of them and its cellular infection
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2018
This study is an extension of our previous paper on the interaction of AcP6-2 and the VIR576 pept... more This study is an extension of our previous paper on the interaction of AcP6-2 and the VIR576 peptides with DPPC: DPPS (3:2) and DMPC: DMPS (3:2) model membranes [Colloids and Surfaces A. 532 (2017) 483-492]. In the present contribution, the temperature effect and the role of the lipid phase in the lipid-peptide interaction were investigated. Moreover at the same time, relating them to HIV-1 FP inhibition. Several biophysics experiments as lipid-peptide binding, Trp fluorescence quenching and Atomic Force Microscopy (AFM) visualization were used to evidence the different interaction of the peptide depending on the physical state of the lipids. In addition, the inhibition effect of HIV-1 FP by P6-2 VIR576 peptide was conducted by fluorescence resonance energy transfer (FRET) and also by AFM microscopy. P6-2VIR576 showed a preference to the liquid crystalline phases from where the peptide can diffuse and interact with the gel phases. Firstly, P6-2VIR576 induces a rigidifying of the membrane to finally, promote the vanishing of these gel phases.
Bollettino chimico farmaceutico
The stability of vinblastine sulphate diluted in 0.9% sodium chloride solution for injection was ... more The stability of vinblastine sulphate diluted in 0.9% sodium chloride solution for injection was studied. Vinblastine sulphate was reconstituted with 0.9% sodium chloride solution for injection to concentration of 1.0 mg/mL and stored in polypropylene syringes at 25 degrees C +/- 1 degree C protected from light. On different days the solutions were analysed and the vinblastine concentration was determined by high-performance liquid chromatography. An high-pressure liquid chromatographic method is described for the quantitative determination of vinblastine in the presence of its degradation products. The degradation of vinblastine was studied by examining the percentage changes from the theoretical concentrations for each solution. The results of these studies indicate that vinblastine solutions in 0.9% sodium chloride solution for injection (1 mg/mL) in polypropylene syringes at 25 degrees C +/- 1 degree C protected from light are stable for up to one month.
Supramolecular Science, Sep 1, 1997
Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The... more Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The synthesis and chemical characterisation of the peptides are described. Physicochemical properties of these peptides such as surface activity, spreadability, monolayer formation, as well as their interaction with lipid monolayers and bilayers, have been studied by using Langmuir-Blodgett films and liposomes as membrane models. In spite of their good water solubility, these peptides are able to form stable monolayers at the air/water interface and to insert into lipid monolayers. The interaction with bilayers is soft; they are not able to induce the leakage of entrapped CF nor to modify the microviscosity of bilayers in general. Thus in these models electrostatic forces apparently do not play an important role, as we expected previously according to the electrical charge of bilayers, markers and peptides.
International Journal of Molecular Sciences, 2021
Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis... more Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.
Nanomaterials, 2020
Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect vari... more Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions wit...
International Journal of Pharmaceutics, 1990
A new method is described for the determination of the broad-spectrum antibiotic Azlocillin sodiu... more A new method is described for the determination of the broad-spectrum antibiotic Azlocillin sodium by HPLC. This method is useful for stability studies, since it allows the separation of Azlocillin from its degradation products. This has been checked by TLC.
Biochimica et biophysica acta, 2015
The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural a... more The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (πe) were clearly lower than the biological membrane pressure (24-30mN m(-1)) and the HIV-1 FP (35mN m(-1)). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (G(E)). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored ...
Colloids and Surfaces A: Physicochemical and Engineering Aspects
Talanta, Jun 13, 2003
Polymyxins are a family of nonribosomic cationic peptide antibiotics highly effective against Gra... more Polymyxins are a family of nonribosomic cationic peptide antibiotics highly effective against Gram-negative bacteria. Two members of this family, Polymyxins B and E (PxB, PxE), form molecular vesicle Á/vesicle contacts and promote a selective exchange of phospholipids at very low concentrations in the membrane, a biophysical phenomenon that can be the basis of their antibiotic mode of action. To get more insight into the interaction of these antibiotics with the lipid membrane, their effect on the structural dynamics of bilayers prepared with lipids extracted from the membrane of Escherichia coli was determined using fluorescently labeled phopholipids. Steady-state anisotropy measurements with probes that localize at different positions in the membrane give information on the effects of polymyxins on the mobility of the phospholipids. Results with PxB, PxE, colymycin M and polymyxin B nonapeptide (PxB-NP), a deacylated derivative with no antibiotic properties, are compared. At low peptide concentrations (B/2 mol%) PxB and PxE bind to the membranes superficially, affecting very slightly the ordering of the lipids at the outermost part of the bilayer. Above this concentration, PxB and PxE insert more deeply in the bilayer, increasing lipid order both in the gel and liquid Á/crystal states and modifying phase transitions. Fluorescence experiments with pyrene labeled phospholipids indicate that the increase in lipid packing is accompanied by an enrichment of phospholipids in the bilayers. In contrast, colymycin M and PxB-NP did not modify lipid packing or phase transition, nor did they induce microdomain formation. The possible significance of these results in the antibiotic mode of action of PxB and PxE is discussed. The combination of spectroscopic techniques described here can be useful as part of a general method of screening for new antibiotics that act on the membrane by the same mechanism as polymyxins.
Journal of Colloid and Interface Science, Aug 1, 2011
The aim of this study was to identify proteins that could inhibit the activity of the peptide seq... more The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2016
CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe sid... more CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated.
Biochimica et biophysica acta, Jan 22, 2015
Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest ... more Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three li...
Pharmaceutica Acta Helvetiae
Bollettino chimico farmaceutico
The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated ... more The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated at different temperatures. The effect of temperature has been determined and from this data, by applying of Arrhenius-law, the stability of azlocillin sodium at 25 degrees C has been predicted and the t90 was determined. Admixtures containing azlocillin sodium (0.01 g ml-1) were prepared in 0.9% sodium chloride injection, in 5% dextrose solution, in 5% levulose solution and in Ringer's lactate solution. The admixtures were stored at 30 degrees, 40 degrees and 50 degrees C in either polyvinyl chloride bags and glass bottles. The change in the initial azlocillin sodium concentration was related to the type of intravenous solution. No dependence with material of container was found. After 24 hours, the change in the initial concentration of penicillin was less than 10% of the initial concentration in 0.9% sodium chloride and 5% levulose solution. However in Ringer's lactate and 5% glucose solution the t90 was lower. These results were found in agreement with experimental ones obtained at room temperature.
Pharmaceutica Acta Helvetiae
International Journal of Molecular Sciences, Apr 29, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Colloids and Surfaces B: Biointerfaces, Aug 1, 2023
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2019
Lipid domains have been obtained using Langmuir-Blodgett films (LBs) and giant unilamellar vesicl... more Lipid domains have been obtained using Langmuir-Blodgett films (LBs) and giant unilamellar vesicles (GUVs). Three membranes compositions were chosen, the canonical DOPC: DOPS (3:2)/SM/CHOL (1:1:1), the more physiological one: DOPC: DOPS (3:2)/SM/CHOL (2:1:1) and another one with more phospholipid content: DOPC: DOPS (3:2)/SM/CHOL (3:1:1). All systems were well characterized by π-A isotherms. As the (SM/CHOL (1:1:1)) concentration increases, the membrane fluidity decreases as demonstrated by the compressibility modulus and area per molecule values. Lipid domains morphology was examined by confocal microscopy. Images corroborated the presence of two liquid immiscible phases: a phospholipid-enriched L d phase and a sphingomyelin enriched L o phase. GBV-C peptide membrane interaction was examined using P6-2VIR576 peptide and tryptophan (Trp) fluorescence spectroscopy. P6-2VIR576 increased the fluidity of lipid monolayers and bilayers making hard to distinguish the L d /L o edges. Its capacity to inhibit the action of the fusion peptide of human immunodeficiency virus (HIV-1 FP) on membranes has been demonstrated. 1. Introduction Eukaryotic cell membranes can exhibit lipid clusters in rafts with different compositions and molecular packing. These rafts play an important role in the assembly of enveloped viruses [1,2]. The human immunodeficiency virus (HIV-1) is one of them and its cellular infection
Colloids and Surfaces A: Physicochemical and Engineering Aspects, 2018
This study is an extension of our previous paper on the interaction of AcP6-2 and the VIR576 pept... more This study is an extension of our previous paper on the interaction of AcP6-2 and the VIR576 peptides with DPPC: DPPS (3:2) and DMPC: DMPS (3:2) model membranes [Colloids and Surfaces A. 532 (2017) 483-492]. In the present contribution, the temperature effect and the role of the lipid phase in the lipid-peptide interaction were investigated. Moreover at the same time, relating them to HIV-1 FP inhibition. Several biophysics experiments as lipid-peptide binding, Trp fluorescence quenching and Atomic Force Microscopy (AFM) visualization were used to evidence the different interaction of the peptide depending on the physical state of the lipids. In addition, the inhibition effect of HIV-1 FP by P6-2 VIR576 peptide was conducted by fluorescence resonance energy transfer (FRET) and also by AFM microscopy. P6-2VIR576 showed a preference to the liquid crystalline phases from where the peptide can diffuse and interact with the gel phases. Firstly, P6-2VIR576 induces a rigidifying of the membrane to finally, promote the vanishing of these gel phases.
Bollettino chimico farmaceutico
The stability of vinblastine sulphate diluted in 0.9% sodium chloride solution for injection was ... more The stability of vinblastine sulphate diluted in 0.9% sodium chloride solution for injection was studied. Vinblastine sulphate was reconstituted with 0.9% sodium chloride solution for injection to concentration of 1.0 mg/mL and stored in polypropylene syringes at 25 degrees C +/- 1 degree C protected from light. On different days the solutions were analysed and the vinblastine concentration was determined by high-performance liquid chromatography. An high-pressure liquid chromatographic method is described for the quantitative determination of vinblastine in the presence of its degradation products. The degradation of vinblastine was studied by examining the percentage changes from the theoretical concentrations for each solution. The results of these studies indicate that vinblastine solutions in 0.9% sodium chloride solution for injection (1 mg/mL) in polypropylene syringes at 25 degrees C +/- 1 degree C protected from light are stable for up to one month.
Supramolecular Science, Sep 1, 1997
Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The... more Four peptide analogues related to the active sequence YIGSR of laminin have been synthesised. The synthesis and chemical characterisation of the peptides are described. Physicochemical properties of these peptides such as surface activity, spreadability, monolayer formation, as well as their interaction with lipid monolayers and bilayers, have been studied by using Langmuir-Blodgett films and liposomes as membrane models. In spite of their good water solubility, these peptides are able to form stable monolayers at the air/water interface and to insert into lipid monolayers. The interaction with bilayers is soft; they are not able to induce the leakage of entrapped CF nor to modify the microviscosity of bilayers in general. Thus in these models electrostatic forces apparently do not play an important role, as we expected previously according to the electrical charge of bilayers, markers and peptides.
International Journal of Molecular Sciences, 2021
Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis... more Research in the pathogenesis of inflammatory skin diseases, such as skin dermatitis and psoriasis, has experienced some relevant breakthroughs in recent years. The understanding of age-related factors, gender, and genetic predisposition of these multifactorial diseases has been instrumental for the development of new pharmacological and technological treatment approaches. In this review, we discuss the molecular mechanisms behind the pathological features of psoriasis, also addressing the currently available treatments and novel therapies that are under clinical trials. Innovative therapies developed over the last 10 years have been researched. In this area, advantages of nanotechnological approaches to provide an effective drug concentration in the disease site are highlighted, together with microneedles as innovative candidates for drug delivery systems in psoriasis and other inflammatory chronic skin diseases.
Nanomaterials, 2020
Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect vari... more Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions wit...
International Journal of Pharmaceutics, 1990
A new method is described for the determination of the broad-spectrum antibiotic Azlocillin sodiu... more A new method is described for the determination of the broad-spectrum antibiotic Azlocillin sodium by HPLC. This method is useful for stability studies, since it allows the separation of Azlocillin from its degradation products. This has been checked by TLC.
Biochimica et biophysica acta, 2015
The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural a... more The interaction between a peptide sequence from GB virus C E1 protein (E1P8) and its structural analogs (E1P8-12), (E1P8-13), and (E1P8-21) with anionic lipid membranes (POPG vesicles and POPG, DPPG or DPPC/DPPG (2:1) monolayers) and their association with HIV-1 fusion peptide (HIV-1 FP) inhibition at the membrane level were studied using biophysical methods. All peptides showed surface activity but leakage experiments in vesicles as well as insertion kinetics in monolayers and lipid/peptide miscibility indicated a low level of interaction: neither E1P8 nor its analogs induced the release of vesicular content and the exclusion pressure values (πe) were clearly lower than the biological membrane pressure (24-30mN m(-1)) and the HIV-1 FP (35mN m(-1)). Miscibility was elucidated in terms of the additivity rule and excess free energy of mixing (G(E)). E1P8, E1P8-12 and E1P8-21 (but not E1P8-13) induced expansion of the POPG monolayer. The mixing process is not thermodynamically favored ...
Colloids and Surfaces A: Physicochemical and Engineering Aspects
Talanta, Jun 13, 2003
Polymyxins are a family of nonribosomic cationic peptide antibiotics highly effective against Gra... more Polymyxins are a family of nonribosomic cationic peptide antibiotics highly effective against Gram-negative bacteria. Two members of this family, Polymyxins B and E (PxB, PxE), form molecular vesicle Á/vesicle contacts and promote a selective exchange of phospholipids at very low concentrations in the membrane, a biophysical phenomenon that can be the basis of their antibiotic mode of action. To get more insight into the interaction of these antibiotics with the lipid membrane, their effect on the structural dynamics of bilayers prepared with lipids extracted from the membrane of Escherichia coli was determined using fluorescently labeled phopholipids. Steady-state anisotropy measurements with probes that localize at different positions in the membrane give information on the effects of polymyxins on the mobility of the phospholipids. Results with PxB, PxE, colymycin M and polymyxin B nonapeptide (PxB-NP), a deacylated derivative with no antibiotic properties, are compared. At low peptide concentrations (B/2 mol%) PxB and PxE bind to the membranes superficially, affecting very slightly the ordering of the lipids at the outermost part of the bilayer. Above this concentration, PxB and PxE insert more deeply in the bilayer, increasing lipid order both in the gel and liquid Á/crystal states and modifying phase transitions. Fluorescence experiments with pyrene labeled phospholipids indicate that the increase in lipid packing is accompanied by an enrichment of phospholipids in the bilayers. In contrast, colymycin M and PxB-NP did not modify lipid packing or phase transition, nor did they induce microdomain formation. The possible significance of these results in the antibiotic mode of action of PxB and PxE is discussed. The combination of spectroscopic techniques described here can be useful as part of a general method of screening for new antibiotics that act on the membrane by the same mechanism as polymyxins.
Journal of Colloid and Interface Science, Aug 1, 2011
The aim of this study was to identify proteins that could inhibit the activity of the peptide seq... more The aim of this study was to identify proteins that could inhibit the activity of the peptide sequence representing the N-terminal of the surface protein gp41 of HIV, corresponding to the fusion peptide of the virus (HIV-1 FP). To do this we synthesized and studied 58 peptides corresponding to the envelope protein E1 of the hepatitis G virus (GBV-C). Five of the E1 synthetic peptides: NCCAPEDIGFCLEGGCLV (P7), APEDIGFCLEGGCLVALG (P8), FCLEGGCLVALGCTICTD (P10), QAGLAVRPGKSAAQLVGE (P18) and AQLVGELGSLYGPLSVSA (P22) were capable of inhibiting the leakage of vesicular contents caused by HIV-1 FP. A series of experiments were carried out to determine how these E1 peptides interact with HIV-1 FP. Our studies analyzed the interactions with and without the presence of lipid membranes. Isothermal titration calorimetry revealed that the binding of P7, P18 and P22 peptides to HIV-1 FP is strongly endothermic, and that binding is entropy-driven. Gibbs energy for the process indicates a spontaneous binding between E1 peptides and HIV-1 FP. Moreover, confocal microscopy of Giant Unilamellar Vesicles revealed that the disruption of the lipid bilayer by HIV-1 FP alone was inhibited by the presence of any of the five selected peptides. Our results highlight that these E1 synthetic peptides could be involved in preventing the entry of HIV-1 by binding to the HIV-1 FP. Therefore, the continued study into the interaction between GBV-C peptides and HIV-1 FP could lead to the development of new therapeutic agents for the treatment of AIDS.
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2016
CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe sid... more CPT-11 and SN-38 are camptothecins with strong antitumor activity. Nevertheless, their severe side effects and the chemical instability of their lactone ring have questioned the usual forms for its administration and have focused the current research on the development of new suitable pharmaceutical formulations. This work presents a biophysical study of the interfacial interactions of CPT-11 and SN-38 with membrane mimetic models by using monolayer techniques and Differential Scanning Calorimetry. The aim is to get new insights for the understanding of the bilayer mechanics after drug incorporation and to optimize the design of drug delivery systems based on the formation of stable bilayer structures. Moreover, from our knowledge, the molecular interactions between camptothecins and phospholipids have not been investigated in detail, despite their importance in the context of drug action. The results show that neither CPT-11 nor SN-38 disturbs the structure of the complex liposome bilayers, despite their different solubility, that CPT-11, positively charged in its piperidine group, interacts electrostatically with DOPS, making stable the incorporation of a high percentage of CPT-11 into liposomes and that SN-38 establishes weak repulsive interactions with lipid molecules that modify the compressibility of the bilayer without affecting significantly neither the lipid collapse pressure nor the miscibility pattern of drug-lipid mixed monolayers. The suitability of a binary and a ternary lipid mixture for encapsulating SN-38 and CPT-11, respectively, has been demonstrated.
Biochimica et biophysica acta, Jan 22, 2015
Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest ... more Resistance to all known antibiotics is a growing concern worldwide, and has renewed the interest in antimicrobial peptides, a structurally diverse class of amphipathic molecules that essentially act on the bacterial membrane. Propelled by the antimicrobial potential of this compound class, we have designed three new lipopeptides derived from polymyxin B, sp-34, sp-96 and sp-100, with potent antimicrobial activity against both Gram positive and Gram negative bacteria. The three peptides bind with high affinity to lipopolysaccharide as demonstrated by monolayer penetration and dansyl-displacement. The interaction with the cytoplasmic membrane has been elucidated by biophysical experiments with model membranes of POPG or POPE/POPG (6:4), mimicking the Gram positive and Gram negative bacterial membrane. Trp-based fluorescence experiments including steady-state, quenching, anisotropy and FRET, reveal selectivity for anionic phospholipids and deep insertion into the membrane. All three li...
Pharmaceutica Acta Helvetiae
Bollettino chimico farmaceutico
The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated ... more The kinetics of degradation of azlocillin sodium in four intravenous admixtures was investigated at different temperatures. The effect of temperature has been determined and from this data, by applying of Arrhenius-law, the stability of azlocillin sodium at 25 degrees C has been predicted and the t90 was determined. Admixtures containing azlocillin sodium (0.01 g ml-1) were prepared in 0.9% sodium chloride injection, in 5% dextrose solution, in 5% levulose solution and in Ringer's lactate solution. The admixtures were stored at 30 degrees, 40 degrees and 50 degrees C in either polyvinyl chloride bags and glass bottles. The change in the initial azlocillin sodium concentration was related to the type of intravenous solution. No dependence with material of container was found. After 24 hours, the change in the initial concentration of penicillin was less than 10% of the initial concentration in 0.9% sodium chloride and 5% levulose solution. However in Ringer's lactate and 5% glucose solution the t90 was lower. These results were found in agreement with experimental ones obtained at room temperature.
Pharmaceutica Acta Helvetiae